TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma

Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ-induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased tumor growth and increased survival. Trem2 inhibition reprogrammed myeloid phenotypes and increased programmed cell death protein 1 (PD-1

The Regulation and Expression of the Creatine Transporter: A Brief Review of Creatine Supplementation in Humans and Animals

Creatine monohydrate has become one of the most popular ergogenic sport supplements used today. It is a nonessential dietary compound that is both endogenously synthesized and naturally ingested through diet. Creatine ingested through supplementation has been observed to be absorbed into the muscle exclusively by means of a creatine transporter, CreaT1. The major rationale of creatine supplementation is to maximize the increase within the intracellular pool of total creatine (creatine + phosphocreatine). There is much evidence indicating that creatine supplementation can improve athletic performance and cellular bioenergetics, although variability does exist. It is hypothesized that this variability is due to the process that controls both the influx and efflux of creatine across the cell membrane, and is likely due to a decrease in activity of the creatine transporter from various compounding factors. Furthermore, additional data suggests that an individual's initial biological profile may partially determine the efficacy of a creatine supplementation protocol. This brief review will examine both animal and human research in relation to the regulation and expression of the creatine transporter (CreaT). The current literature is very preliminary in regards to examining how creatine supplementation affects CreaT expression while concomitantly following a resistance training regimen. In conclusion, it is prudent that future research begin to examine CreaT expression due to creatine supplementation in humans in much the same way as in animal models

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

The effects of a creatine supplement formulation containing cinnamon extract on creatine uptake, creatine transporter expression, insulin signaling, and muscle performance in males.

Includes bibliographical references (p. 124-128).Creatine monohydrate has become one of the most popular ingested nutritional supplements used for its potential to enhance athletic performance. Numerous creatine formulations have been developed to maximize creatine absorption, and may also provide a means to either partially bypass or up-regulate the function of creatine transporter-1 (CreaT1). Cinnamon extract (Cinnulin) has been observed to mimic the effects of insulin, thereby up-regulating glucose uptake and insulin signaling. This study examined how a seven-week supplementation regimen with creatine monohydrate combined with Cinnulin (CCI), creatine monohydrate (CR), or placebo (PLA) affected physiological and molecular adaptations in nonresistance-trained males following a prescribed resistance-training program. Results demonstrated that Cinnulin combined with creatine monohydrate elicited greater mean increases in relative 1-RM leg press, thigh lean mass, body water, and total Akt protein content when compared to creatine monohydrate alone, or placebo; however, intramuscular creatine increases between the CCI and CR groups demonstrated no significant differences.by Ryan D. Schoch.M.S.Ed

The effects of a creatine supplement formulation containing cinnamon extract on creatine uptake, creatine transporter expression, insulin signaling, and muscle performance in males.

Includes bibliographical references (p. 124-128).Creatine monohydrate has become one of the most popular ingested nutritional supplements used for its potential to enhance athletic performance. Numerous creatine formulations have been developed to maximize creatine absorption, and may also provide a means to either partially bypass or up-regulate the function of creatine transporter-1 (CreaT1). Cinnamon extract (Cinnulin) has been observed to mimic the effects of insulin, thereby up-regulating glucose uptake and insulin signaling. This study examined how a seven-week supplementation regimen with creatine monohydrate combined with Cinnulin (CCI), creatine monohydrate (CR), or placebo (PLA) affected physiological and molecular adaptations in nonresistance-trained males following a prescribed resistance-training program. Results demonstrated that Cinnulin combined with creatine monohydrate elicited greater mean increases in relative 1-RM leg press, thigh lean mass, body water, and total Akt protein content when compared to creatine monohydrate alone, or placebo; however, intramuscular creatine increases between the CCI and CR groups demonstrated no significant differences.by Ryan D. Schoch.M.S.Ed